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Human
Disease
Articles
Labcoats
at Work
Getting Real About Getting into Science
A
Genetic Journey
Ting Ting Zhang
GENETICS is the science of heredity. It is important to biology because genes are the principal determinants of all life processes, from cell structure and function to reproduction of the organism. A genetic disease can be the result of mutations at the DNA level (Molecular Genetics) or mutations at the chromosome level (Cytogenetics). The Prince of Wales Hospital has developed a connection between patients and the medical community through genetic counselling and provided a laboratory service for the screening of genetic diseases.
The first step of the journey for a prospective parent concerned about hereditary diseases is to contact a genetic counsellor. The counsellor in the hospital will firstly provide basic information about genetics to the patient, such as “what are chromosomes?”. They will also gather a family history from the patient to create a brief family pedigree. This shows who is likely to be a carrier of a genetic disorder and the probability that their children will have the disorder as well.
Early detection of a genetic disease is done by recognising heterozygotes (carriers) of recessive mutations, and by fetal analysis. Specimens like amniotic fluid (the fluid that the embryo is suspended in) for prenatal diagnosis, and blood drawing and tissue samples for chromosome analysis, are collected at the Central Sample Reception. Such specimens are then grouped and transferred to the Molecular Genetics and Cytogenetics department. Today’s journey will bring us to look at the cytogenetic part of the laboratory in Prince of Wales Hospital.
Dr. Michael Burkley, the head of Molecular Genetics and Cytogenetics of SEALS in the hospital explains, “Cytogenetics is the study of chromosomes and chromosome abnormalities. In addition, everything in cytogenetics is cultured, because the cells arriving in test samples are much fewer than the cells we need to look at.” Cells are set up in a culture media and incubated for a few days to allow the cells to grow to a significant number for harvest. In order to capture the cells in metaphase (cell division), where chromosomes are visible and highly condensed as sister chromatids (“daughter” strands of the replicated chromosome), the cells are “fixed” by a variety of processes for cytogenetic analysis.
At the sub-chromosomal level, low-resolution physical mapping has produced a map of human chromosomes. In the procedure of “G-banding”, metaphase chromosomes are first treated with mild heat or proteolytic enzymes to partially digest the chromosomal proteins, which helps to make the chromosome easier to analyse. Then, a Giemsa stain is used to produce dark banding patterns that are seen under the microscope. Stains are specific for individual chromosomes, allowing for the identification of each chromosome. This selective staining makes it possible to recognise structural abnormalities associated with specific genetic syndromes.
Another procedure, called “fluorescence” in-situ hybridization (FISH), uses light – fluorescence -- instead of dark banding, and it yields higher resolution. Metaphase chromosomes are fixed onto a microscope slide and are treated to cause the two strands of DNA’s double helix to separate. Specific DNA sequences are then cloned and tagged with fluorescent chemicals that have different colours from different DNA sequences. The tagged DNA sequences, called DNA probes, are added to the chromosomes where they will bind to the region from which they were cloned. The position where the probes have bound to the chromosomes can be observed by using fluorescence and digital imaging microscopy – essentially, computer imaging analysis of the sample examined under a fluorescence microscope. This has been useful in detecting abnormalities beyond the resolution level of studying banded chromosomes at the microscope and also in determining the location of specific genes on chromosomes.
The reports of chromosomal information are then sent to Michael to ensure that the details and interpretation are correct. These results will provide extra information for a genetic counsellor or medical practitioner to convey to the patient. Genetic counselling includes evaluation of the risk that prospective parents may produce a child with a genetic disorder and presentation of options to family members. A genetic counsellor helps the patient understand the risks associated with birth defects and hereditary disorders by interpreting family history, laboratory results and other medical information. “Experiences are a heavy component of counseling. You can’t look at the text book for answers. Can you?” says Carolyn Francis, one of the genetic counsellors. “We also provide support for the patients”.
Cytogenetic
analysis has been an invaluable tool in screening, diagnosing and counseling
on genetic disorders. In the future, cytogenetic methods will become progressively
linked to molecular techniques and will continue to play an important
role in medical service and research.
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Media
Culturing example
Microscopy analysis
Genetic counselling